Functional polymorphism of CYCLE underlies the diapause variation in moths

• Published in: Science (American Association for the Advancement of Science) Vol. 388; no. 6750; p. eado2129
• Main Authors: Zheng, Shirui, Wang, Yaohui, Li, Guiyun, Qin, Sheng, Dong, Zhi, Yang, Xu, Xu, Xiaomiao, Fang, Gangqi, Li, Muwang, Zhan, Shuai
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 29.05.2025
• Subjects: Adaptation; Alleles; Animals; BMAL1 protein; Bombyx - embryology; Bombyx - genetics; Bombyx - physiology; Bombyx mori; Butterflies & moths; Changing environments; Circadian rhythm; Circadian Rhythm - genetics; Circadian rhythms; Climate change; Clock gene; CLOCK Proteins - chemistry; CLOCK Proteins - genetics; Diapause; Diapause, Insect - genetics; Domestication; Dormancy; Environmental changes; Environmental conditions; Frameshift mutation; Gene deletion; Gene loci; Genetic crosses; Genetic diversity; Genome-Wide Association Study; Genomes; Global climate; Hibernation; Insect Proteins - chemistry; Insect Proteins - genetics; Insects; Isoforms; Lepidoptera; Life history; Loci; Molecular modelling; Mutagenesis; Mutation; Phenotype; Phenotypes; Polymorphism; Polymorphism, Genetic; Protein Isoforms - genetics; Range extension; Silk; Speciation; Species; Tropical environment; Tropical environments; Vertebrates
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.ado2129

Diapause is a common seasonal adaptive strategy that regulates annual timing in insects. Very few causal loci underlying diapause variation have yet been identified. By leveraging cross-mapping and genome-wide association analysis, we identified the N terminus of the clock protein CYCLE as a major causal effector underlying embryonic diapause differences in the silk moth. We found that the nondiapause phenotype in polyvoltine strains results from a specific deletion that disrupts an alternative isoform of CYCLE. We further demonstrated that different CYCLE isoforms contribute to a functional diversity in modulating circadian rhythms and diapause, which has been preserved in Lepidoptera for at least 110 million years. Our study proposes a model that explains how adaptive phenotypes can evolve rapidly without affecting related essential functions. Akin to hibernation in other species, diapause allows insects to remain dormant through harsh seasons. Zheng et al . examined the genetic basis of this trait in silk moths ( Bombyx mori ), the strains of which vary in their diapause timing and expression. Several genomic loci associated with this variation, including a peak encompassing the gene Cycle . This transcription factor is well known for its importance in circadian rhythms across species. Strains lacking the diapause phenotype altogether were homozygous for a frameshift mutation that completely disrupted a single isoform of Cycle . Given the conservation of Cycle across Lepidoptera (moths and butterflies), this gene may control diapause more broadly. —Corinne Simonti